The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has a mission to develop safe and effective contraceptives for women, including obese women. Obesity is the number one public health issue facing the US population and is an independent risk for venous thromboembolism (VTE). Therefore, there is a public health need to develop effective contraception for woman that does not increase the risk of VTE. One Food and Drug Administration (FDA)-approved contraceptive method is the progestin-only pill (POP). This method requires strict adherence to taking the POP at the same time every day. The method is associated with irregular bleeding which often leads to discontinuation of the method. Daily low dose oral progesterone receptor modulators (PR.WlS) , such as UPA, have been shown to inhibit ovulation and cause amenorrhea. The endogenous estrogen level is not affected by the PRM. Thus, the method will provide a regimen that is easier to follow than a POP regimen and have a theoretically lower risk of VTE, especially for obese women. In addition, there is in vitro evidence that UP A may have protective activity against breast cancer. In order to provide preliminary evidence that daily, low dose UP A could be effective for contraception, a clinical trial will be conducted in the NICHD Contraceptive Clinical Trials Network (CCTN). The proposed study will be evaluated sequentially. Initially, women of reproductive age, with normal menstrual cycles, will receive treatment for 12 weeks (three 28-day cycles) in order to evaluate the mechanisms of contraceptive efficacy, safety and acceptability of this new contraceptive. Subjects will be randomized into 3 arms: ? Group 1: UP A 5 mg taken orally daily for 24 days followed by a pill-free interval of 4 days, repeated 3 times. ? Group 2: UP A 10 mg taken orally daily for 84 days (12 weeks) without interruption. ? Group 3: UPA 5 mg taken orally daily for 84 days (12 weeks) without interruption.